The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity

FEBS Lett. 2010 Jul 2;584(13):2845-51. doi: 10.1016/j.febslet.2010.04.068. Epub 2010 May 4.


Farnesoid X receptor (FXR) is highly expressed in liver and intestine where it controls bile acid (BA), lipid and glucose homeostasis. Here we show that FXR is expressed and functional, as assessed by target gene expression analysis, in human islets and beta-cell lines. FXR is predominantly cytosolic-localized in the islets of lean mice, but nuclear in obese mice. Compared to FXR+/+ mice, FXR-/- mice display a normal architecture and beta-cell mass but the expression of certain islet-specific genes is altered. Moreover, glucose-stimulated insulin secretion (GSIS) is impaired in the islets of FXR-/- mice. Finally, FXR activation protects human islets from lipotoxicity and ameliorates their secretory index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Humans
  • In Vitro Techniques
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism*
  • Isoxazoles / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Obesity / metabolism
  • Palmitic Acid / pharmacology*
  • Rats
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Cytoplasmic and Nuclear / physiology*


  • Isoxazoles
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Palmitic Acid
  • GW 4064